1. Field of the Invention
The present invention is directed to a process for the synthesis of 2,2,6,6-tetramethyl-4-oxopiperidine, which is also known as 2,2,6,6-tetramethyl-4-piperidone and triacetonamine. For convenience, the compound will be referred to hereinafter as triacetonamine. More particularly, the present invention is directed to a process that can be carried out at room temperature for the synthesis of triacetonamine with high selectivity by reacting an acetone compound with an ammonia source in the presence of a calcium-containing catalyst.
2. Description of Related Art
Triacetonamine is a known compound that is useful as an intermediate in the preparation of drugs and 2,2,6,6-tetramethyl piperidyl and related light stabilizers for polymeric materials. Its structural formula is: 
An outline of how triacetonamine is used as an intermediate in the preparation of stabilizers appears in U.S. Pat. No. 4,124,564.
Triacetonamine has been known at least since the work of Heinz, Annalen der Chemie, 203:336 (1880). Heinz converted acetone to phorone in about 30% yield and reacted the phorone with ammonia to yield triacetonamine in 70% yield.
Hall, Journal of the American Chemical Society, 79:5447 (1957) disclosed reacting acetone with ammonia in the presence of calcium chloride for nine days, thereby obtaining a yield of about 20% of triacetonamine after careful fractional distillation.
More specifically, Hall passed ammonia into a mixture of acetone and CaCl2 for 30 minutes. Additional ammonia was added for 15-minute periods at intervals of 3 hours for five days. After four days of standing at room temperature, the mixture was dark and syrupy, but the calcium chloride had not liquefied. It was poured into 50% NaOH and then the upper layer was decanted from the heavy white sludge of calcium hydroxide, which was then rinsed with ether until tests with ethereal picric acid indicated the absence of amines in the extract. The combined ether layers were dried over K2CO3 and distilled to give a yellow liquid. Careful fractionation of this material through a spinning band column gave 666 g (20.0%) of triacetonamine.
Sosnovsky et al., Synthesis 11:735-6 (1976) describe a method for the preparation of triacetonamine in yields of 70-89% (taking into account recovered acetone) from acetone, ammonia, and calcium chloride using easily accessible laboratory equipment.
Wu et al., Synthetic Communications 226(19):3565-3569 (1996) describe a method for the preparation of triacetonamine in which p-nitrotoluene is used as a catalyst. Yields of triacetonamine of up to 65% are reported.
Bradbury et al., Journal of the Chemical Society, 1394-99 (1947) describe reactions of acetone and ammonia, alone and with a number of different catalysts, that did not give any triacetonamine. Bradbury""s product, obtained in 17% yield without catalyst and in 35% to 90% yield depending on catalyst choice, was 2,2,4,4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine hydrate, split to diacetonamine oxalate by the action of alcoholic oxalic acid.
U.S. Pat. No. 1,473,285 discloses the formation of a mixture of acetone amines such as diacetone amine, triacetone diamine, triacetone amine, and other products by the action of ammonia on acetone at high temperatures (100xc2x0 C.) or at ordinary temperature after long standing. It is disclosed that the use of dehydrating agents such as calcium chloride greatly facilitates the reaction and also gives a product of greater value as an accelerator.
U.S. Pat. No. 3,513,170 discloses a process for the preparation of 2,2-dimethyl-4-oxo-6,6-disubstituted piperidine derivatives which comprises reacting diacetone alcohol with ammonia and a ketone derivative in the presence of a Lewis acid. This patent also discloses a process for the preparation of triacetonamine which comprises reacting 2,2,4,4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine with a Lewis acid in the presence of water. The compounds are said to be useful as intermediates for the synthesis of light stabilizers for polyolefins.
U.S. Pat. No. 3,943,139 discloses the preparation of triacetonamine by heating phorone with aqueous ammonia and basic catalysts, such as lithium, sodium, calcium, or barium hydroxide, in an autoclave under pressure.
U.S. Pat. No. 3,953,459 discloses the preparation of triacetonamine from 2,2,4,4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine by treatment with an acidic catalyst. Suitable catalysts are Lewis acids, protonic acids and their salts with ammonia or organic bases. The reaction may be carried out in organic solvents, preferably in acetone, by gentle heating, for example at 40xc2x0 to 65xc2x0 C. Yields of 95% are said to be obtainable after a reaction of several hours.
U.S. Pat. No. 3,959,295 discloses the preparation of triacetonamine from acetone and ammonia in the presence of acidic catalysts. Suitable catalysts are Lewis acids, protonic acids and their salts with ammonia or with organic bases, as for example BF3, NH4Cl, or H2SO4. The addition of an alcohol, such as methanol, as well as the use of a cocatalyst may promote the reaction. The process may be carried out in two steps, in the first of which the temperature is held below 35xc2x0 C. In the second step, a further amount of acetone is added and the temperature is raised to about 40xc2x0 to 65xc2x0 C.
U.S. Pat. No. 3,959,298 discloses a process for preparing triacetonamine characterized in that acetonine is reacted with water in the presence of at least 12.5 mole % based on acetonine of an acid catalyst.
U.S. Pat. No. 3,960,875 discloses the preparation of triacetonamine from 2,2,4,4,6-pentamethyl-2,3,4,5-tetramethylpyrimidine (acetonine) by heating in the presence of acetone, diacetone alcohol or water. These reagents may be used in excess or an organic solvent is added. The preferred modification is the heating of acetonine hydrate in an excess of acetone or in an acetone-methanol mixture to about 40xc2x0 to 65xc2x0 C. for several hours. The use of diacetone alcohol is said to permit higher reaction temperatures leading to shorter reaction times.
U.S. Pat. No. 3,963,730 discloses a process for preparing triacetonamine, characterized in that acetonine is reacted with acetone in the presence of at least 12.5 mol % based on acetonine of an acid catalyst under anhydrous conditions.
U.S. Pat. No. 4,252,958 discloses a process for preparing triacetonamine in which a hydrazine hydrohalide salt catalyzes the reaction of an acetone compound, for example acetone or diacetone alcohol, with an ammonia donor compound, for example ammonia or acetonine.
U.S. Pat. No. 4,275,211 discloses a process for producing piperidines, including, inter alia, tiacetonamine, wherein a catalyst is used that is a strongly acid ion exchanger having a medium or large mesh size or having large macropores.
U.S. Pat. No. 4,356,308 discloses the synthesis of triacetonamine from acetone and ammonia wherein a partially halogenated or perhalogenated aliphatic or cyclic hydrocarbon is used as catalyst in an amount of from 0.01 to 5 mol %, relative to acetone.
U.S. Pat. No. 4,418,196 discloses process for preparing triacetonamine by reacting acetone and/or an acid condensate of acetone with ammonia in the presence of at least one catalyst selected from the group consisting of organotin halides, 1,3,5,2,4,6-triazatriphosphorin hexahalides and cyanuric halides.
U.S. Pat. No. 4,536,581 discloses a process for preparing triacetonamine from ammonia and acetone, wherein acetone and ammonia are reacted in a single stage for a time of 2 to 8 hours in an acetone:ammonia molar ratio of 20:1 to 4:1, at a temperature of 50xc2x0 to 120xc2x0 C. and at a pressure of 1 to 50 atmospheres, in the presence of 0.001-0.1 mole of acid catalysts per mole of acetone used in the reaction.
U.S. Pat. No. 4,663,459 discloses a process for the preparation of triacetonamine by reacting acetone with ammonia in the presence of a catalytically effective amount of an organic carboxylic acid halide.
U.S. Pat. No. 4,831,146 discloses a process for producing 2,2,6,6-tetraalkyl-4-oxopiperidines by the reaction of a ketone and ammonia. Ammonium hydroxide can be substituted for the ammonia. A catalytic amount of a super acid, i.e., a perfluorinated sulfonic acid polymer or perfluorinated alkyl sulfonic acid is used as the catalyst. Typically, the catalyst is supported on a porous inert solid having a pore diameter of between 50 and 600 Angstroms or higher and typically are inorganic oxides such as alumina, fluorided alumina, zirconia, silica, silica-alumina, bauxite, kieselguhr, kaolin, charcoal, porous glass, etc.
Russian Certificate of Invention No. 473,715 discloses a process for the preparation of triacetonamine by reacting acetone with ammonium carbonate in the presence of calcium chloride and subsequently isolating the end product according to known methods.
Polish Provisional Patent No. 118,992 discloses a method for synthesizing triacetonamine by reaction of acetone with ammonium chloride, which closes the ring, in the presence of calcium oxide. The reaction is conducted at a temperature around 50xc2x0 C. in the presence of about 10 vol. % of water relative to the acetone used.
Hungarian Patent Disclosure No. 46,306 discloses a process for preparing triacetonamine by reacting acetone and ammonia in the presence of ammonium chloride catalyst, characterized in that the ammonia is introduced into the reaction mixture in the form of an aqueous ammonium hydroxide solution.
Japanese Patent Disclosure No.: Sho 63-[1988]-222,157 discloses a method for the synthesis of triacetonamine, characterized in that acetone and (or) an acidic condensation product of acetone and ammonia are reacted at a temperature in the range of 0-60xc2x0 C. in the presence of more that 12.5 mol. %, in relation to the amounts of acetone and (or) an acidic condensation product of acetone and ammonia used, of an acid catalyst selected from among an inorganic acid, a carboxylic acid, a sulfonic acid, and a salt of these acids with ammonia or a nitrogen-containing organic base. Additional amounts of acetone and (or) the acidic condensation product of acetone are then added and the reaction is heated to complete the reaction.
W. Heintz, Ammoniakderivate des Acetons, Annalen 174, 133 (1874) saturated acetone with ammonia and heated at 100xc2x0 C. in a sealed tube. A mixture of diacetoneamine and triacetoneamine with some other amines was obtained. Heintz correctly deduced the structure of TAA.
E. Matter, Uber ein Neues Reaction Product aus Aceton und Ammonia, Helv. Chim. Acta XXV 1114-1122 (1947) allowed acetone/ammonia 1:1.9 to stand 12 hours at 27-29xc2x0 C. over mixture of CaClz and NH4Cl. They obtained an 82% yield of acetonin based on aetone. They demonstrated that acetonin hydrolyzed rapidly to diacetoneamine in the presence of aqueous HCl. They also were able to isolate acetonin hydrate as a discrete compound.
Keisuke Murayama et al. (Sankyo) Stable Free Radicals I. Synthesis of 2,2,6,6-tetramethyl-4-piperidone, Nippon Kagaku Zasshi 1969, 90(3) 296 (Japan) treated acetone with ammonia in presence of Calcium Chloride.
The disclosures of the foregoing are incorporated herein by reference in their entirety.
The present invention relates to a process that can be carried out at room temperature for the synthesis of triacetonamine with high selectivity by reacting an acetone compound with an ammonia source in a single step in the presence of a calcium-containing catalyst.
More particularly, the present invention relates to a process for the synthesis of 2,2,6,6-tetramethyl-4-oxopiperidine comprising reacting in a liquid phase reaction mixture:
A) at least one acetone compound selected from the group consisting of acetone, a condensation product of acetone with itself, and a condensation product of acetone with ammonia, and
B) at least one ammonia donor compound not identical with the acetone compound selected from the group consisting of ammonia and a condensation product of acetone with ammonia, in the presence of a catalytically effective amount of a crystalline aluminosilicate containing calcium.
In a highly preferred embodiment, the present invention is directed to a process for the synthesis of 2,2,6,6-tetramethyl-4-oxopiperidine comprising reacting in a liquid phase reaction mixture in a single step at a temperature maintained in the range of from about 20xc2x0 C. to about 25xc2x0 C.:
A) acetone,
B) ammonium nitrate, and
C) ammonium hydroxide
in the presence of a catalytically effective amount of a CaY zeolite;
wherein the molar ratio of acetone to the combination of ammonium nitrate and ammonium hydroxide is within the range of from about 1:1 to about 20:1 and the amount of CaY zeolite is within the range of from about 0.01 to about 10% by weight of the acetone.
In another preferred embodiment, the present invention is directed to a process for the synthesis of 2,2,6,6-tetramethyl-4-oxopiperidine which comprises reacting in a liquid phase reaction mixture:
A) at least one acetone compound; and
B) a combination of two ammonia compounds comprising ammonium nitrate and ammonia,
in the presence of a catalytically effective amount of a crystalline aluminosilicate containing calcium, to form a reaction mixture;
wherein the ammonia is added to the reaction mixture in gaseous form, more preferably, wherein the ammonia in gaseous form is continuously added to the reaction mixture.
The acetone compound starting material for the synthesis of triacetonamine by the process of the present invention can be acetone; a condensation product of acetone with itself, such as diacetone alcohol, mesityl oxide, phorone, and the like; a condensation product of acetone with ammonia, such as diacetonamine, triacetonediamine, acetonine, and the like; or mixtures of the foregoing. Preferably, the acetone compound is acetone.
The ammonia donor compound starting material can be ammonia; ammonium hydroxide; a condensation product of acetone with ammonia, such as diacetonamine, triacetonediamine, acetonine, and the like; an ammonium salt of an inorganic or an organic acid, such as ammonium nitrate, ammonium chloride, ammonium bromide, ammonium iodide, ammonium sulfate, ammonium acetate, ammonium propionate, ammonium oxalate, ammonium maleate, ammonium succinate, and the like; or mixtures of the foregoing. Ammonium hydroxide and ammonium nitrate are preferred and their use in combination is most preferred. Particularly preferred is the combination of ammonia in gaseous form and ammonium nitrate.
Some combinations of starting materials that can be used according to this invention to prepare triacetonamine in the presence of a calcium-containing molecular sieve catalyst include acetone with ammonia, diacetone alcohol with ammonia; acetonine with ammonia; acetone with diacetonamine; acetone with acetonine; mesityl oxide with acetonine; diacetone alcohol with triacetonediamine; acetone with ammonia and acetonine; mesityl oxide and phorone with ammonia; diacetone alcohol and mesityl oxide with ammonia and diacetonamine; and, preferably, acetone with ammonium hydroxide and ammonium nitrate.
The relative proportions of acetone compound and ammonia donor compound can be varied over a wide range. The molar ratio of acetone compound to ammonia donor compound can, for example, be within the range of from about 1:1 to about 20:1, preferably from about 2:1 to about 10:1, most preferably from about 3:1 to about 6:1.
Catalysts to be used in the process of this invention comprise specific crystalline aluminosilicates, namely, X and Y zeolites. Crystalline aluminosilicates, or zeolites, can be in the form of agglomerates having high physical strength and attrition resistance. Methods for forming the crystalline powders into such agglomerates include the addition of an inorganic binder, generally a clay comprising a silicon dioxide and aluminum oxide, to the high purity zeolite powder in wet mixture. The blended clay zeolite mixture is extruded into cylindrical type pellets or formed into beads which are subsequently calcined in order to convert the clay to an amorphous binder of considerable mechanical strength. As binders, clays of the kaolin type, water permeable organic polymers or silica are generally used.
The zeolites have known cage structures in which the alumina and silica tetrahedra are intimately connected in an open three-dimensional network to form cage-like structures with window-like pores. The tetrahedra are cross-linked by the sharing of oxygen atoms with spaces between the tetrahedra occupied by water molecules prior to partial or total dehydration of the zeolite. The dehydration of the zeolite results in crystals interlaced with cells having molecular dimensions and thus, the crystalline aluminosilicates are often referred to as xe2x80x9cmolecular sievesxe2x80x9d when they effect separation that is dependent essentially upon differences between the sizes of the feed molecules.
In hydrated form, crystalline aluminosilicates include type X zeolites, represented by Formula I below in terms of moles of oxides:
(0.9xc2x10.2)M2/nO:Al2O3:(2.5xc2x10.5)SiO2:yH2Oxe2x80x83xe2x80x83(I)
where xe2x80x9cMxe2x80x9d is a cation having a valence of not more than 3 that balances the electrovalence of the tetrahedra and is generally referred to as an exchangeable cation, xe2x80x9cnxe2x80x9d represents the valence of the cation, and xe2x80x9cyxe2x80x9d, which represents the moles of water, is a value up to about 9 depending upon the identity of xe2x80x9cMxe2x80x9d and the degree of hydration of the crystal. As noted from Formula I, the SiO2/Al2O3 mole ratio is 2.5xc2x10.5. As the X zeolite is initially prepared, the cation xe2x80x9cMxe2x80x9d is usually predominately sodium, that is, the major cation at the exchangeable cationic sites is sodium and the zeolite is therefore referred to as a sodium-X zeolite. Depending upon the purity of the reactants used to make the zeolite, however, cations other than sodium may be present as impurities, such as barium, lithium, copper, potassium, calcium, and mixtures thereof.
The type Y structured zeolite, in the hydrated or partially hydrated form, can be similarly represented in terms of moles of oxides as in Formula II below:
(0.9xc2x10.2)M2/nO:Al2O3:wSiO2:yH2Oxe2x80x83xe2x80x83(II)
where xe2x80x9cMxe2x80x9d, xe2x80x9cnxe2x80x9d and xe2x80x9cyxe2x80x9d are the same as above and xe2x80x9cwxe2x80x9d is a value greater than about 3 up to about 6. The SiO2/Al2O3 mole ratio for type Y structured zeolites can thus be from about 3 to about 6. For both zeolites, the cation xe2x80x9cMxe2x80x9d may be one or more of a variety of cations but, as the Y type zeolites are initially prepared, the cation xe2x80x9cMxe2x80x9d is also usually predominately sodium. The type Y zeolite containing predominately sodium cations at the exchangeable cationic sites is, therefore, referred to as a sodium-exchanged type-Y, or NaY, zeolite. Depending upon the purity of the reactants used to make the zeolite, however, cations other than sodium may be present as impurities, such as barium, lithium, copper, potassium, calcium, and mixtures thereof. It is highly preferred in the practice of the present invention that calcium be present in the crystalline aluminosilicate, either as an impurity or by exchange. Most preferably, the catalyst employed in the practice of the present invention is a calcium-exchanged type-Y, or CaY, zeolite.
The optimum quantity of zeolite catalyst employed in a given embodiment of the present invention can easily be determined by those skilled in the art by routine experimentation. Generally, the amount of catalyst will be within the range of from about 0.01 to about 10% by weight of the acetone compound, preferably from about 0.1 to about 5%.
A solvent or diluent is not necessary in the process of this invention, but one can be used, if desired. The solvent should be inert, and have a boiling temperature at or above the selected reaction temperature. Solvents that can be used include, for example, aliphatic hydrocarbons, such as pentane, hexane, heptane; aromatic hydrocarbons, such as benzene, toluene, xylene; chlorinated aliphatic and aromatic hydrocarbons, such as methylene chloride, trichloroethane, chloroform, carbon tetrachloride; chlorobenzene, the dichlorobenzenes and trichlorobenzenes; the chlorotoluenes and the chloroxylenes; aliphatic and cycloaliphatic alcohols, such as methanol, ethanol, isopropanol, butanol, t-butanol, 2-ethylhexanol, cyclohexanol; and aliphatic and heterocyclic ethers, such as diethyl ether, tetrahydrofuran and dioxane. Normally, the reaction will be run in the presence of excess acetone, which, in such instance, can act as a solvent as well as a reactant.
In the synthesis of triacetonamine according to the process of this invention, the presence of water is not detrimental. Some water is formed as a product of the reaction between acetone and ammonia and such water can, if desired, be removed as it forms, or allowed to accumulate and become part of the solvent system.
The reactants, catalyst, solvent and so on can be charged all at once or in several portions as the reaction proceeds. Ammonia in gaseous form can be added to the reaction mixture continuously as the reaction proceeds.
Neither reaction temperature nor reaction pressure is critical. The process of the invention will proceed at room temperature or below, as well as at elevated temperatures. Preferably, the reaction temperature is within the range from about 0xc2x0 C. and the boiling point of the reaction mixture at atmospheric pressure, more preferably in the range of from about 0xc2x0 C. to about 50xc2x0 C., to about with ambient temperature, i.e., a range of from about 20xc2x0 to about 25xc2x0 C., particularly preferred. If the reaction mixture boils at 60xc2x0 C. or below, the reaction temperature can, if desired, be increased to from 60xc2x0 to about 110xc2x0 C. by applying superatmospheric pressures of up to about 30 atmospheres, preferably up to about 5 atmospheres.
The required reaction time ranges from about 1 to about 24 hours, preferably from about 2 to about 17 hours, more preferably from about 2 to about 6 hours. Those skilled in the art will readily understand that reaction times can be shortened by elevation of reaction temperatures.
As a practical matter, in one embodiment, the reaction can be carried out in a single step in a very simple manner by simply combining the reagents and stirring the mixture. The reaction does not require either heating or cooling, unless desired, because the mixture will heat spontaneously to a temperature in the range of from about 38xc2x0 to about 56xc2x0 C. owing to the heat of the reaction.
At the end of the reaction, the lowest boiling components of the mixture are unreacted acetone, water, and solvent, if used; these can be stripped off and used as the solvent or diluent in subsequent preparations without separation from one another. Triacetonamine can be recovered from the reaction mixture by conventional techniques, for example, by precipitation as the hydrate by adding water; by precipitation as the hydrohalide, sulfate, or oxalate salt by adding the appropriate acid; or by distillation, suitably after adding an excess of strong alkali, such as concentrated aqueous potassium or sodium hydroxide solution.
The advantages and the important features of the present invention will be more apparent from the following examples.